Tourette Syndrome (TS) is a common genetic neurological disease that begins in childhood, and is manifest as the inability to keep from making repetitive, stereotyped sounds and movements (i.e., phonic and motor tics) over long periods of time. The objective of this research is to use behavior and neuroimaging tools to analyze functional brain networks in children with TS. The focus is on regional functional interactions in the brain, as well as the activity level within individual regions, and how they may be altered after treatment with standard TS medications, such as neuroleptics and centrally acting adrenergic agents. Despite knowledge of the pharmacologic properties of these therapeutic agents, we do not know how they affect brain functioning in TS. Our previous work (Church et al., 2009, Brain;Baym et al. 2008, Brain) has suggested that TS impairs task control networks of the brain, particularly affecting regions involved in adaptive control. This proposal examines whether TS medication improves the profile of activity in these adaptive control regions, as well as in the frontal and subcortical regions thought to play a role in TS. The proposed study will utilize a repeated measures design, collecting brain scans of children with TS prior to and during medication use, during rest, and during performance of a rule-switching task. Control groups of unaffected children and unmedicated children with TS will be scanned over the same time interval. Regional or network changes after medication use in the TS group may reveal where in the brain the medications are having the greatest functional influence. We can also gauge whether the brain activity in children with TS post- medication looks more similar to that of healthy age-matched children or whether there is evidence of compensatory activation of an alternative network. This study takes a first step towards addressing some of the difficulties facing studies of developmental disorders (e.g. symptom severity, medication use, and age-related changes). The proposed multifaceted approach in children with TS should inform both our understanding of the disorder and the influence of common TS treatments on the brain. This neuroimaging and behavioral study should help to disentangle the effects of TS, per se, versus the effects of pharmacotherapy for TS, on brain functioning. If successful, the lessons from the proposed study will have implications for understanding other pediatric neuropsychiatric disorders and their treatments. PUBLIC HEALTH RELEVANCE: This neuroimaging and behavioral study should help to disentangle the effects of TS, per se, versus the effects of pharmacotherapy for TS, on brain functioning. If successful, the lessons from the proposed study will have implications for understanding other pediatric neuropsychiatric disorders and their treatments.